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- W2158160931 abstract "Today there is no therapeutics to treat or prevent Alzheimer's disease (AD). Inflammation, and particularly TNF alpha (TNFa) signaling, plays a major role in the progression of AD neuropathology. Preliminary results indicated that chronic TNFa inhibition by thalidomide significantly reduces brain TNFa, BACE1, and Aß levels, as well as significantly reduces plaque burden in APP23 transgenic mice. However, in a human AD pilot trial that we are conducting, 10 of 10 patients on thalidomide experienced adverse events, and six of these events were serious enough to require removal from the study. Therefore, we hypothesized that lenalidomide, a less toxic analog of thalidomide, might represent a safer alternative to treat AD. As proof of concept of lenalidomide efficacy, we performed a pilot study on a few APP23 mice. The effects of three doses of lenalidomide were evaluated: 0, 10, or 100 mg/kg administered intraperitoneally for four weeks to APP23 mice (n = 2, 2, and 3, respectively). After sacrifice, the brain of each mouse was hemisected and used in histological and biochemical experiments. Brain sections were immunostained with an anti-Aß antibody (6E10) and counterstained with thioflavin S. Western blots for TNFa precursor and BACE1 (two BACE1 antibodies: N-terminal and C-terminal) proteins were conducted on brain lysates. APP23 mice treated with 10 and 100 mg/kg lenalidomide showed ∼70% decrease in total (dense + diffuse plaques; 6E10 immunostainging) and dense (thioflavine-S positive) cortical amyloid plaques compared to vehicle-treated animals. The immunomodulatory efficacy of lenalidomide treatment was confirmed by a 25% decrease in brain TNFa precursor levels measured by Western blot. In addition, Western blotting also revealed a 50% decrease in BACE1 signals after lenalidomide treatment." @default.
- W2158160931 created "2016-06-24" @default.
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- W2158160931 date "2012-07-01" @default.
- W2158160931 modified "2023-09-27" @default.
- W2158160931 title "P1-216: Preclinical testing of lenalidomide as anti-amyloid treatment for Alzheimer's disease" @default.
- W2158160931 doi "https://doi.org/10.1016/j.jalz.2012.05.495" @default.
- W2158160931 hasPublicationYear "2012" @default.
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